When human heart muscle cells derived from embryonic stem cells are
implanted into a rat after a heart attack, they can help rebuild the
animal's heart muscle and improve function of the organ, scientists
report in the September issue of Nature Biotechnology. The researchers
also developed a new process that greatly improves how stem cells are
turned into heart muscle cells and then survive after being implanted
in the damaged rat heart. The findings suggest that stem-cell-based
treatments might one day help people suffering from heart disease, the
leading cause of death in most of the world.

The study was
conducted by researchers at the University of Washington School of
Medicine in Seattle and at Geron Corp. in Menlo Park, Calif. The
scientists set out to tackle two of the main challenges to treating
damaged hearts with stem cells: the creation of cardiac cells from
embryonic stem cells, and the survival of those cells once they are
implanted in a damaged heart.

"Past attempts at treating
infarcted hearts with stem cells have shown promise, but they have
really been hampered by these challenges," explained Dr. Chuck Murry,
director of the Center for Cardiovascular Biology in the UW Institute
for Stem Cell and Regenerative Medicine, and corresponding author on
the study. "This method we developed goes a long way towards solving
both of those problems. We got stem cells to differentiate into mostly
cardiac muscle cells, and then got those cardiac cells to survive and
thrive in the damaged rat heart."

Embryonic stem cells can
differentiate, or turn into, any type of cell found in the body. But
researchers had struggled to get stem cells to differentiate into just
cardiomyocytes, or heart muscle cells -- most previous efforts resulted
in cell preparations in which only a fraction of 1 percent of the
differentiated cells were cardiac muscle cells. By treating the stem
cells with two growth factors, or growth-encouraging proteins, and then
purifying the cells, they were able to turn about 90 percent of stem
cells into cardiomyocytes.

The researchers dealt with the
other big challenge of stem cell death by implanting the cells along
with a cocktail of compounds aimed at helping them grow. The cocktail
included a growth "matrix"-- a sort of scaffolding for the cells to
latch on to as they grow -- and drugs that block processes related to
cell death. When using the pro-growth cocktail, the success rate of
heart muscle grafts improved drastically: 100 percent of rat hearts
showed successful tissue grafts, compared to only 18 percent in grafts
without the cocktail.

"The problem of cell death is pretty
common in stem-cell treatments," Murry explained. "When we try to
regenerate with liquid tissues, like blood or bone marrow, we're pretty
good at it, but we haven't been very successful with solid tissues like
skeletal muscle, brain tissue, or heart muscle. This is one of the most
successful attempts so far using cells to repair solid tissues -- every
one of the treated hearts had a well-developed tissue graft."

When
the researchers followed up on the stem-cell treatment by taking images
of the rat hearts, they found that the grafts helped thicken the walls
that normally stretch out after a heart attack and cause the heart to
weaken. The thickened walls were also associated with more vigorous
contraction.

"We found that the grafts didn't just survive
in the rat hearts -- they also helped improve the function of the
damaged heart," said Dr. Michael Laflamme, UW assistant professor of
pathology and the lead author of the study. "That's very important,
because one of the major problems for people suffering a myocardial
infarction is that the heart is damaged and doesn't pump blood nearly
as well. This sort of treatment could help the heart rebound from an
infarction and retain more of its function afterwards."

The
next step in studying stem-cell treatments for the heart is to conduct
similar experiments in large animals, like pigs or sheep, while further
refining the treatment in rats. Early human clinical trials could begin
in about two years, Murry said.